LECT2, also known as leukocyte cell-derived chemotaxin 2 or chondromodulin II (ChM-II), is a 16-kDa protein mainly produced by hepatocytes. It was initially identified as a neutrophil chemotactic factor. LECT2 binds to several cell-surface receptors like CD209a, Tie1, and Met, regulating various pathways such as PPAR signaling. It has pleiotropic functions in physiological and pathological processes, including liver regeneration, neuronal development, and homeostasis of haematopoietic stem cells (HSC), as well as in diseases like liver injury, fibrosis, hepatocellular carcinoma, metabolic disorders, and inflammatory arthritides [2,3].

In liver fibrosis, LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, while these changes are reversed in Lect2-KO mice. AAV9-LECT2 shRNA treatment significantly attenuates fibrosis, indicating that targeting LECT2/Tie1 signaling may be a potential therapeutic approach for liver fibrosis, and serum LECT2 level could be a biomarker for its screening and diagnosis [1]. In a male mouse model of LPS-mediated NASH, LECT2 deletion exacerbates liver steatosis and macrophage infiltration, suggesting that LECT2 might protect against lipid accumulation and macrophage activation in the liver, potentially via p38 phosphorylation [4].

In conclusion, LECT2 is a multifunctional protein involved in various biological processes and disease conditions. Studies using Lect2-KO mouse models have revealed its crucial roles in liver-related diseases such as fibrosis and NASH, highlighting its potential as a biomarker and therapeutic target in these disease areas.